The long term goal of this work is to provide a clearer understanding of the regulation and function of specific stress proteins in the ischemic heart. The overall hypothesis of the proposed work is that member(s) of the family of heat shock transcription factors exert complementary roles to activate stress proteins which attenuate cellular damage to the myocardium during ischemia and reperfusion. To test this hypothesis, we propose the following three specific aims: 1) To determine in vivo the precise temporal and spatial patterns of Hsp7o and Hsc70 mRNA expression within specific myocardial cells after bona fide myocardial ischemia. 2) To create mice deficient for heat shock transcriptional factors, mHSF1 and mHSF2, by gene-targeting in murine embryonic stem (ES) cells. 3) To elucidate more precisely the biological and functional role(s) of each specific HSF (aim2) during ischemia in transgenic mice.